Hydromorphone and hydrocodone are opioid analgesic drugs available in the market and both are generally used for relief of moderate to severe pain in patients where an opioid analgesic is appropriate. Hydrocodone is the most frequently prescribed opiate in the United States. Although hydromorphone is two to three times more potent than hydrocodone, it is also at least two to four times more expensive than hydrocodone. The higher cost of hydromorphone is due to the difficulty of its production. Despite this, however, prescriptions for hydromorphone products increased from about 0.47 million in 1998 to about 1.83 million in 2006. The aggregate production quota for hydromorphone as established by DEA increased from 766 kilograms in 1998 to 3,300 kilograms in 2006.
One of the current methods for the production of hydromorphone or hydrocodone involves a two-step oxidation/reduction route from morphine or codeine, respectively. This method, however, is expensive, low yielding, and forms impurities that are difficult to remove. Another production method involves the isomerization of morphine to hydromorphone in the presence of a late transition metal and a metal chloride. This method is also low yielding because significant amounts of impurities are generated. Moreover, the products have high levels of metal contamination. Thus, there is a need for new processes for producing hydromorphone or hydrocodone at lower costs, with higher yields and higher purity to meet the increasing demand for these analgesics.